This invention relates to the use of an irreversible inhibitor of GABA-transaminase for the treatment of substance addiction and modification of behavior associated with substance addiction. More specifically, the invention relates to the treatment of phencyclidine addiction and modification of behavior associated with phencyclidine addiction.
Phencyclidine, better known as PCP, is an illegal synthetic drug. Unlike cocaine and THC which are derived from natural sources, PCP is made from industrial chemicals.
PCP was developed in the 1950""s as an intravenous anesthetic. Use of PCP in humans was discontinued in 1965, because it was found that patients often became agitated, delusional and irrational while recovering from its anesthetic effects. PCP is illegally manufactured in laboratories and is sold on the street by such names as xe2x80x9cangel dustxe2x80x9d, xe2x80x9cozonexe2x80x9d, xe2x80x9cwackxe2x80x9d, and xe2x80x9crocket fuelxe2x80x9d. xe2x80x9cKiller jointsxe2x80x9d and xe2x80x9ccrystal supergrassxe2x80x9d are names that refer to PCP combined with marijuana. The variety of street names for PCP reflects its bizarre and volatile effects.
PCP is a white crystalline powder that is readily soluble in water or alcohol. It has a distinctive bitter chemical taste. PCP can be mixed easily with dyes and turns up on the elicit drug market in a variety of tablets, capsules, and colored powders. It is normally used in one of three ways: snorted, smoked, or ingested. For smoking, PCP is often applied to a leafy material such as mint, parsley, oregano or marijuana.
PCP interrupts the functions of the neocortex, the section of the brain that controls the intellect and keeps instincts in check. Because the drug blocks pain receptors, violent PCP episodes may result in self-inflicted injuries. The effects of PCP vary, but users frequently report a sense of distance and estrangement. Time and body movements are slowed down. Muscular coordination worsens and senses are dulled. Speech is blocked and incoherent. In later stages of chronic use, users often exhibit paranoid and violent behavior and experience hallucinations. Large doses may produce convulsions and coma, as well as heart and lung failure.
PCP is addicting. There is evidence of both physical and psychological dependence upon PCP. Use of PCP often leads to psychological dependence, craving, and compulsive PCP-seeking behavior.
Many PCP users are brought to emergency rooms because of PCP""s adverse psychological effects or because of overdoses. In a hospital or detention setting, PCP users often become violent or suicidal, and are very dangerous to themselves and to others.
At low to moderate doses, physiological effects of PCP include a slight increase in breathing rate and a more pronounced rise in blood pressure and pulse rate. Respiration becomes shallow, and flushing and profuse sweating occur. Generalized numbness of the extremities and muscular incoordination also may occur. The psychological effects include distinct changes in body awareness, similar to those associated with alcohol intoxication. Use of PCP among adolescents may interfere with hormones related to normal growth and development as well as the learning process.
At high doses of PCP, there is a drop in blood pressure, pulse rate, and registration. This may be accompanied by nausea, vomiting, blurred vision, flicking up and down of the eyes, drooling, loss of balance, and dizziness. High doses of PCP can also cause seizures, coma and death. The psychological effects at high doses include illusions and hallucinations. PCP can cause effects that mimic the full range of symptoms of schizophrenia, such as delusions, paranoia, disordered thinking, a sensation of distance from ones"" environment, and catatonia. Speech is often sparse and garbled.
People who use PCP for long periods report memory loss, difficulties with speech and thinking, depression and weight loss. These symptoms can persist up to a year after sustained PCP use. Mood disorders also have been reported. PCP has sedative effects, and interactions with other central nervous system depressants, such as alcohol and benzodiazepines, can lead to coma or accidental overdose.
It has been found that addicting drugs such as nicotine, cocaine and PCP enhance dopamine (DA) within the mesotelencephalic reward/reinforcement circuitry of the forebrain, presumably producing the enhanced brain reward that consistutes the drug user""s xe2x80x9chighxe2x80x9d. Alterations in the functions of the dopamine (DA) systems have also been implicated in drug craving and in relapse to the drug-taking habit in recovering addicts. For example, cocaine acts on these DA systems by binding to the dopamine transporter (DAT) and preventing DA reuptake into the presynaptic terminal. There is considerable evidence that the addictive liability of addicting drugs is linked to the reuptake blockade in central nervous system (CNS) reward/reinforcement pathways.
There are currently no medications approved by the food and drug administration (FDA) for treating addiction to PCP. There are medications, however, for treating the adverse health effects of using PCP. Generally, there are two types of medications that are used to treat PCP abuse. They are anti-anxiety medications such as diazeparn, better known as Valium(copyright). Anti-anxiety medications are administered when the PCP user experiences delusional symptoms, hallucinations, or feels paranoid. However, such medications only treat the symptoms as opposed to the addiction itself.
Thus, there remains a need in the treatment of addiction to PCP which can relieve a patient""s craving by changing the pharmacological actions of PCP in the central nervous system.
The present invention, which addresses the needs of the prior art, provides methods for treating substance addiction and changing addiction-related behavior of a mammal, for example a primate, suffering from phencyclidine (PCP) addiction by administering to the mammal an effective amount of a pharmaceutical composition or medicament which includes gamma vinyl GABA (GVG). The amount of GVG varies from about 15 mg/kg to about 2 gm/kg, preferably from about 100 mg/kg to about 600 mg/kg, and most preferably from about 150 mg/kg to about 300 mg/kg.
In another embodiment, the present invention provides a method for changing addiction-related behavior of a mammal suffering from addiction to PCP which comprises administering to the mammal an effective amount of GVG or a pharmaceutically acceptable salt thereof, wherein the effective amount attenuates the rewarding/incentive effects of PCP in the absence of altering rewarding/incentive effects of food in said mammal.
The amount of GVG varies from about 15 mg/kg to about 2 gm/kg, preferably from about 15 mg/kg to about 600 mg/kg, and most preferably from about 150 mg to about 600 mg/kg.
As a result of the present invention, methods of reducing PCP addiction and changing addiction-related behavior are provided which are based on a pharmaceutical composition or medicament which is not itself addictive, yet is highly effective in reducing the addiction and the addictive behavior of addicted patients. The pharmaceutical composition or medicament useful for the method of the present invention inhibits or eliminates craving experienced by PCP addicts. Moreover, the reduction of behavior associated with PCP addiction occurs in the absence of an aversive or appetitive response to GVG. Moreover, behavior characteristics associated with dependency on PCP are reduced or eliminated in the absence of an alteration in the locomotor function of the primate.
In yet another embodiment, the invention includes a method for changing addiction-related behavior of a mammal suffering from addiction to PCP which comprises administering to the mammal an effective amount of GVG or a pharmaceutically acceptable salt thereof, or an enantiomer or a racemic mixture thereof, wherein the effective amount is sufficient to diminish, inhibit or eliminate behavior associated with craving or use of PCP.
In another exemplary embodiment of the present invention, the method includes changing addiction-related behavior of a mammal suffering from addiction to PCP which comprises administering to the mammal an effective amount of a composition or medicament that increases central nervous system GABA levels, wherein the effective amount is sufficient to diminish, inhibit or eliminate behavior associated with craving or use of PCP.
Other improvements which the present invention provides over the prior art will be identified as a result of the following description which sets forth the preferred embodiments of the present invention. The description is not in any way intended to limit the scope of the present invention, but rather only to provide a working example of the present preferred embodiments. The scope of the present invention will be pointed out in the appended claims.